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Published on: July 24, 2018
Analysis of how melatonin-upregulated clock genes PER2 and CRY2 alleviate rheumatoid arthritis-associated
Yinping Huo1, Yajie Gao2, Bingle Li3
1The Central Lab, the First Affiliated Hospital of Baotou Medical College, Baotou, 014010, China; Department of Rheumatology and Immunology, the First Affiliated Hospital of Baotou Medical College, Baotou, 014010, China.
Abstract:
Melatonin (Mel) serves as the central regulator for maintaining circadian rhythms and plays a crucial role not only in controlling the rhythmic clock, but also in several functional domains such as immunomodulation and anti-inflammation. In this study, we explored the clinical relevance of Mel and rheumatoid arthritis comorbid with interstitial lung disease (RA-ILD), and its potential therapeutic effects on arthropathy and pulmonary fibrosis (PF) in mice with collagen-induced arthritis (CIA). The results demonstrated that low serum levels of Mel were correlated with disease activity and severity of PF in RA-ILD patients. In addition, Mel was potentially efficacious in alleviating arthritis, bone destruction, and PF in a mouse model of CIA. Meanwhile, we observed that in lung tissues, the circadian-clock genes (CCGs) period circadian regulator 2 (PER2) and cryptochrome circadian regulator 2 (CRY2) were predominantly expressed in epithelial cells (ECs), and the regulation of their expression in ECs was closely correlated with Mel-mediated suppression of inflammatory responses and a significant reduction in macrophagic inflammatory activity. These results implied that Mel and its associated CCGs might play important regulatory roles in RA-ILD and its associated pathological processes.
Insights
Low melatonin levels are linked to rheumatoid arthritis with interstitial lung disease (RA-ILD) severity. Melatonin shows potential therapeutic effects against arthritis and lung fibrosis in mouse models.
Area of Science:
- Immunology
- Rheumatology
- Pulmonology
- Chronobiology
Background:
- Melatonin (Mel) is a key regulator of circadian rhythms, influencing immunomodulation and anti-inflammation.
- Rheumatoid arthritis comorbid with interstitial lung disease (RA-ILD) presents complex pathological processes.
- Circadian-clock genes (CCGs) are implicated in various physiological functions.
Purpose of the Study:
- To investigate the clinical relevance of melatonin in RA-ILD patients.
- To evaluate the therapeutic potential of melatonin in a mouse model of collagen-induced arthritis (CIA).
- To explore the role of melatonin and CCGs in RA-ILD pathogenesis.
Main Methods:
- Analysis of serum melatonin levels in RA-ILD patients.
- Assessment of melatonin's effects on arthritis and pulmonary fibrosis (PF) in CIA mice.
- Examination of circadian-clock gene expression (PER2, CRY2) in lung tissues.
Main Results:
- Low serum melatonin levels correlated with disease activity and PF severity in RA-ILD patients.
- Melatonin demonstrated efficacy in alleviating arthritis, bone destruction, and PF in CIA mice.
- Melatonin regulated CCG expression (PER2, CRY2) in lung epithelial cells, suppressing inflammation.
Conclusions:
- Melatonin deficiency is associated with RA-ILD.
- Melatonin holds therapeutic promise for RA-ILD, impacting both arthropathy and pulmonary fibrosis.
- Melatonin and its associated CCGs may be critical regulators in RA-ILD pathogenesis.
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